On November 5, 2019 PureTech Health plc (LSE: PRTC) ("PureTech"), a clinical-stage biotechnology company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, reported the presentation of new preclinical data from its wholly-owned immuno-oncology programs at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting in National Harbor, Md (Press release, PureTech Health, NOV 5, 2019, View Source [SID1234550362]).

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The two scientific posters detail the Company’s continued progress in advancing two fully human monoclonal antibodies (mAbs) developed to inhibit two foundational immunosuppressive orchestrators, galectin-9 (LYT-200) and pathogenic gamma delta-1 (γδ1) T cells (LYT-210).

"These data further show the unique position and importance of galectin-9 and γδ1 as immunosuppressors in cancer biology. Both have been observed to have powerful properties to disable immune-mediated cancer attack, which may explain some of the fundamental efficacy limitations of other immuno-oncology therapies," said Joseph Bolen, PhD, chief scientific officer at PureTech. "Our novel antibodies targeting galectin-9 and γδ1 have produced compelling single-agent preclinical data against a number of difficult-to-treat cancers in models where approved immunotherapies haven’t worked. We are excited to share our continued progress with the scientific community at premier conferences such as SITC (Free SITC Whitepaper)."

The new data presented at SITC (Free SITC Whitepaper) indicate that galectin-9 is not only a potent therapeutic target, but also a potentially relevant biomarker. Across multiple cohorts, galectin-9 was significantly increased in blood samples of individuals with primary and metastatic pancreatic cancer, lung tumors, and colorectal carcinoma, compared to healthy individuals.

"These findings validate the importance of galectin-9 in cancer biology and its potency as a target," said George Miller, MD, Director of S. Arthur Localio Laboratories and Director of the Cancer Immunology Program at NYU School of Medicine and a PureTech collaborator. "Our research indicates that galectin-9 is a master immunosuppressor; it induces a highly favorable microenvironment for tumor growth. LYT-200 has potential both as a single agent and in combination with checkpoint inhibitors to have therapeutic potential by reversing the immunosuppression which can be present in the tumor microenvironment."

PureTech expects to file an Investigational New Drug application (IND) for LYT-200 in the first half of 2020 and to initiate a Phase 1a/1b clinical trial in solid tumors in 2020. The mAb has been tested as a single agent as well as in combination with anti-PD1 checkpoint inhibitors in preclinical murine and human-derived ex vivo models, showing robust and reproducible activity, immune activation potential as well as excellent drug properties.

PureTech also presented data on its monoclonal antibody LYT-210 that targets γδ1 T cells whose immunosuppressive features leads to a tumor permissive microenvironment. The research presented at SITC (Free SITC Whitepaper) showed that γδ1 T cells were the most abundant T cell within the studied tumors, which included pancreatic, colorectal, cholangiocarcinoma, and liver cancer, and represented up to 50% of all infiltrating T cells. PureTech also presented data showing that LYT-210 depletes immunosuppressive γδ1 T cells through cytotoxicity and phagocytosis. Together, these findings further support the ability of LYT-210 to potentially restore the immune system’s ability to fight difficult-to-treat cancers. PureTech expects to file an IND for LYT-210 in 2021 for solid tumors.

"These data show that γδ1 cells play a key role in suppressing the immune system’s ability to attack tumors. LYT-210 is designed to remove and destroy pathogenic γδ1 T cells enabling immune mediated cancer attack. We therefore believe LYT-210 holds significant promise as a potential immunotherapy," said Dr. Miller.